The long-range aim of the proposed research is to understand the role central nervous system neurotransmitter systems play in the mediation of the actions of psychotropic drugs and in the maintenance of behavior. We will focus on dopamine, norepinephrine, 5-hydroxytryptamine and gamma amino butyric acid, and their relationship to operant behavior. Feeding, drinking and locomotion will also be studied since they are important components of operant behavior. The actions of neurotransmitters will be modified by drugs and/or neurotoxins. Behavior will be measured using computer-oriented techniques. There are two broadly defined foci of the current application. First, we will attempt to identify changes in neurotransmitter systems that occur when operant behavior is modified by administration of antidepressant drugs. The goal of this research is to elucidate changes in central nervous system neurochemistry which lead to changes in behavior and which may be involved in the pathophysiology of depression. Second, we will attempt to identify the neurochemical mechanisms in the central nervous system that account for drug-behavior-environment interactions to further understand the relative roles of drugs and the environment in modifications of behavior.